title: DNA/long peptide vaccination against conserved regions of SIV induces partial protection against SIVmac251 challenge.
abstract: OBJECTIVE
  We recently developed a HIVconsv vaccine strategy, consisting of combined conserved regions of HIV-1, to adequately cover viral diversity. To evaluate efficacy in nonhuman primates, an equivalent SIV-derived immunogen SIVconsv was designed and delivered as plasmid DNA or synthetic long peptides.
  
  
  METHODS
  Rhesus macaques lacking protective MHC class I alleles Mamu-A*001 : 01, B*008 : 01, B*017 : 01 were immunized with either SIVconsv synthetic long peptides (S) alone or in combination with plasmid DNA encoding the same conserved regions (D) using SSS or DDSS regimens.
  
  
  METHODS
  The SIVconsv synthetic long peptide vaccine consisted of 46 approximately 30-amino acid-long peptides emulsified in Montanide ISA-720 and adjuvanted with pegylated type I interferon and imiquimod.
  
  
  RESULTS
  Both SSS and DDSS regimens generated high frequencies of SIV-specific IFN-γ-producing cells comparable with reported adenoviral vector systems. Strong polyfunctional CD4⁺ T-cell and modest CD8⁺ T-cell responses were generated, which were of central memory T-cell phenotype. Furthermore, SIVconsv-specific antibody responses were induced capable of recognizing the Env glycoprotein. Eight weeks after the last immunization, control and SIVconsv-vaccinated animals were challenged intrarectally with 10 MID50 of pathogenic SIVmac251. Two out of six animals in the DDSS group were protected against infection, while all 14 animals in the SSS and two control groups were infected. Vaccine induced SIV-specific IgG responses in mucosal washes prechallenge were highest in the two protected animals.
  
  
  CONCLUSIONS
  This study demonstrates that vaccine-elicited responses towards conserved regions can afford partial protection against a high-dose intrarectal SIVmac251 challenge.
authors.affiliation: aDepartment of Virology bDepartment of Comparative Genetics and Refinement, Biomedical Primate Research Centre, Rijswijk cDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands dUniversity of Regensburg, Regensburg, Germany eThe Jenner Institute, University of Oxford, Oxford, UK fISA Pharmaceuticals, Leiden, the Netherlands.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Koopman
authors.forename: Niels
authors.initials: N
authors.lastname: Beenhakker
authors.forename: Ivonne
authors.initials: I
authors.lastname: Nieuwenhuis
authors.forename: Gaby
authors.initials: G
authors.lastname: Doxiadis
authors.forename: Petra
authors.initials: P
authors.lastname: Mooij
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Josef
authors.initials: J
authors.lastname: Koestler
authors.forename: Tomas
authors.initials: T
authors.lastname: Hanke
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fagrouch
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Verschoor
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Bontrop
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
authors.forename: Willy M J M
authors.initials: WM
authors.lastname: Bogers
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic